大麻素通过CB1依赖的和CB1独立的肠表皮的途径阻断脂肪诱导的胰岛素释放
Pedro Antonio Perez1,2, Mark Benjamin Wiley1, Alexandros Makriyannis3
1Center for Cannabinoid Research (UCRCCR), School of Medicine, University of California, Riverside, Riverside, California.
Gastro hep advances
|September 25, 2024
概括
大麻素受体激动剂通过差异性抑制cretin释放. 一些影响涉及肠道大麻素受体1 (CB1R) 信号传递,而另一些影响独立于肠道CB1Rs,影响葡萄糖平衡.
科学领域:
- 内分泌学和新陈代谢学
- 胃肠道生理学 胃肠道生理学
- 神经内分泌学神经内分泌学
背景情况:
- 葡萄糖平衡依赖于胃岛轴,涉及来自肠道细胞的GLP1和GIP等激素.
- 素 (GLP1,GIP) 调节胰岛素的释放和食欲;相关的治疗方法针对2型糖尿病和肥胖症.
- 大麻素受体1 (CB1R) 存在于产生隐素的细胞中,但其在脂肪诱导的隐素释放中的作用尚不清楚.
研究的目的:
- 调查肠上皮细胞CB1Rs在调节脂肪诱导的隐素分泌中的作用.
- 为了确定大麻素受体激动剂是否通过CB1R依赖和不依赖的途径对cretin释放产生差异影响.
主要方法:
- 使用了在肠表皮质中有条件删除CB1Rs的小鼠 (IntCB1-/-) 和对照 (IntCB1+/+).
- 小鼠接受了油,以刺激胰岛素的释放,并给予CB1R激动剂 (WIN55,212-2,THC) 和抗剂 (AM6545).
- 测量了生物活性GLP1和GIP的血水平.
主要成果:
- 口服脂肪刺激了对照小鼠的GLP1和GIP释放.
- 在对照小鼠中,WIN55,212-2和THC抑制了脂肪诱导的隐形蛋白释放,AM6545.5部分逆转了这种效应.
- 在IntCB1-/-小鼠中,WIN55,212-2抑制了GLP1,但没有抑制GIP的释放,而THC则无论肠道CB1R状态如何,都抑制了这两种隐形素.
结论:
- 大麻素受体激动剂可以通过肠道CB1R依赖和不依赖的机制抑制隐素的释放.
- 这些发现凸显了大麻素对隐素分泌的复杂调节,这与代谢障碍有关.
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